A Genetic Model of Perinatal Iron Deficiency

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DESCRIPTION (provided by applicant): The goal of this project is to evaluate the structural and behavioral effects of region and temporally specific iron deficiency (ID) on the developing hippocampus in a mouse conditional knockout model. The hippocampus is widely recognized as having paramount importance in several cognitive functions, including learning and memory. Unfortunately, the hippocampus is more susceptible than other brain areas during the perinatal period to many insults such as ID (Erickson et al, 1997). ID is the most prevalent micronutrient deficiency in the world, and affects some 250,000 neonates each year in the USA alone. Cognitive deficits resulting from perinatal ID persist into adulthood (Lozoff et al, 2000). Animal studies utilizing dietary restriction (which is a different etiology of ID than is seen in humans in the US) of iron have shown structural, biochemical, and cognitive impairments, but fail to clarify whether the effect on the hippocampus is indeed due to ID in the cells comprising the hippocampus, or due to other pathophysiological states that occur in conjunction with dietary ID (anemia, hypoxia). We are using a conditional KO model of an iron transporter (DMT1), and will examine its effects on structural and behavioral phenotypes related to learning & memory.